Abstract
Luteoloside is a member of the flavonoids family that exhibits several bioactivities including anti-microbial and anti-cancer activities. However, the antiviral activity of luteoloside against enterovirus 71 (EV71) and the potential mechanism(s) responsible for this effect remain unknown. In this study, the antiviral potency of luteoloside against EV71 and its inhibitory effects on 3C protease activity were evaluated. First, we investigated the cytotoxicity of luteoloside against rhabdomyosarcoma (RD) cells, which was the cell line selected for an in vitro infection model. In a subsequent antiviral assay, the cytopathic effect of EV71 was significantly and dose-dependently relieved by the administration of luteoloside (EC50 = 0.43 mM, selection index = 5.3). Using a plaque reduction assay, we administered luteoloside at various time points and found that the compound reduced EV71 viability in RD cells rather than increasing defensive mobilization or viral absorption. Moreover, biochemical studies focused on VP1 (a key structural protein of EV71) mRNA transcript and protein levels also revealed the inhibitory effects of luteoloside on the EV71 viral yield. Finally, we performed inhibition assays using luteoloside to evaluate its effect on recombinant 3C protease activity. Our results demonstrated that luteoloside blocked 3C protease enzymatic activity in a dose-dependent manner (IC50 = 0.36 mM) that was similar to the effect of rutin, which is a well-known C3 protease inhibitor. Collectively, the results from this study indicate that luteoloside can block 3C protease activity and subsequently inhibit EV71 production in vitro.
Highlights
Luteoloside is a member of the flavonoids family and was extracted from several traditional Chinese herbs [1,2,3,4] and other plants [5,6]
To clarify whether the inhibitory activity of luteoloside against enterovirus 71 (EV71) was associated with its toxicity to the cells, the viabilities of RD cells were examined 48 h after luteoloside administration
Lonicera japonica is a well-known traditional Chinese herb that has been widely used in HFMD treatments [38] due to its antiviral activity against HFMD pathogens, including coxsackievirus [39]
Summary
Luteoloside is a member of the flavonoids family and was extracted from several traditional Chinese herbs [1,2,3,4] and other plants [5,6]. Previous studies have reported the potential bioactivities of luteoloside, which include anti-microbial activity [3], the inhibition of melanogenesis [5], the suppression of proliferation [7], and anti-cancer activity [8]. Flavonoids exhibit broadspectrum antiviral effects against influenza virus [2], human rhinovirus [9], poliovirus [10,11,12,13], coxsackievirus B4, echovirus 6, and enterovirus 71 (EV71) [11]. Studies focused on the antiviral efficacy of luteoloside against EV71 are limited.
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